How do I interpret hepatitis C lab results and what are the treatment options for a patient with a positive HCV (Hepatitis C Virus) antibody test?

Hepatitis C Lab Interpretation and Treatment Options

For patients with a positive HCV antibody test, confirmatory HCV RNA testing is essential to determine current infection status and guide treatment decisions. 1

Interpreting HCV Test Results

Initial HCV Antibody Testing

When a patient has a positive HCV antibody test, this indicates one of three possibilities:

1. Current HCV infection
2. Past HCV infection that has resolved
3. False positive result

The signal-to-cutoff (S/CO) ratio from the antibody test provides valuable information:

• Very low S/CO ratio: Likely false positive, no further testing needed
• Low S/CO ratio: Possible false positive, immunoblot testing recommended
• High S/CO ratio: Likely true positive, proceed directly to HCV RNA testing 2

Confirmatory Testing Algorithm

Test Outcome	Interpretation	Further Action
HCV antibody nonreactive	No HCV antibody detected	No further action required unless recent exposure suspected
HCV antibody reactive	Presumptive HCV infection	Test for HCV RNA to identify current infection
HCV antibody reactive, HCV RNA detected	Current HCV infection	Provide counseling and link to medical care and treatment
HCV antibody reactive, HCV RNA not detected	No current HCV infection	No further action in most cases; consider second antibody test if distinction between resolved infection and false positive is desired [1]

Special Testing Considerations

• For suspected recent exposure (within past 6 months): Test for HCV RNA even with negative antibody
• For immunocompromised patients: Consider HCV RNA testing regardless of antibody result
• Before starting antiviral therapy: Confirm HCV RNA positivity with a second blood sample 1

Treatment Options for Confirmed HCV Infection

For patients with confirmed current HCV infection (HCV RNA positive), direct-acting antiviral (DAA) therapy is the standard of care:

First-Line Treatment Option

Ledipasvir/Sofosbuvir (HARVONI) is a highly effective treatment option:

• Dosing: One tablet (90mg ledipasvir/400mg sofosbuvir) daily with or without food 3
• Duration: Typically 12 weeks, though duration may vary based on patient characteristics
• Renal considerations: No dosage adjustment required for any degree of renal impairment, including ESRD on dialysis 3

Monitoring During Treatment

• Confirm HCV RNA positivity before initiating therapy
• Test for HBV coinfection (HBsAg and anti-HBc) before starting treatment due to risk of HBV reactivation 3, 4
• Monitor for signs of hepatitis flare or HBV reactivation during treatment if HBV coinfected
• Be alert for symptomatic bradycardia if patient is taking amiodarone (coadministration not recommended) 3, 4

Common Side Effects

The most common adverse events with sofosbuvir-based regimens include:

• Fatigue (38%)
• Headache (24%)
• Nausea (22%)
• Insomnia (15%) 4

Important Clinical Considerations

Reporting Requirements

• Positive HCV antibody and RNA results are reportable to health departments in most jurisdictions 1
• "Acute hepatitis C" and "hepatitis C (past or present)" are nationally notifiable conditions 1

Birth Cohort Considerations

• Persons born between 1945-1965 represent the majority of HCV cases (67.2% of HCV RNA positive cases) 5
• This birth cohort should be prioritized for screening and linkage to care

Common Pitfalls to Avoid

1. Not confirming active infection: Approximately 50% of persons reported with positive HCV antibody do not have confirmatory RNA testing 5
2. Misinterpreting antibody-only results: A positive antibody test alone cannot distinguish between current and past infection
3. Failing to screen for HBV coinfection: HBV reactivation can occur during HCV treatment, potentially leading to fulminant hepatitis, liver failure, and death 3, 4
4. Drug interactions: P-gp inducers (e.g., rifampin, St. John's wort) can significantly decrease ledipasvir and sofosbuvir plasma concentrations, reducing therapeutic effect 3, 4

By following this structured approach to HCV testing and treatment, clinicians can accurately diagnose current HCV infections and provide appropriate care to improve patient outcomes and reduce morbidity and mortality.